2HHH

Crystal structure of kasugamycin bound to the 30S ribosomal subunit

Summary for 2HHH

• Entry DOI: 10.2210/pdb2hhh/pdb
• Descriptor: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (22 entities in total)
• Functional Keywords: ribosome, 30s, antibiotics, initiation
• Biological source: Thermus thermophilus; More
• Total number of polymer chains: 21
• Total formula weight: 784440.75

Authors

Schluenzen, F. (deposition date: 2006-06-28, release date: 2006-09-26, Last modification date: 2024-04-03)

Primary citation

Schluenzen, F.,Takemoto, C.,Wilson, D.N.,Kaminishi, T.,Harms, J.M.,Hanawa-Suetsugu, K.,Szaflarski, W.,Kawazoe, M.,Shirouzo, M.,Nierhaus, K.H.,Yokoyama, S.,Fucini, P.
The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation.
Nat.Struct.Mol.Biol., 13:871-878, 2006

PubMed Abstract: Kasugamycin (Ksg) specifically inhibits translation initiation of canonical but not of leaderless messenger RNAs. Ksg inhibition is thought to occur by direct competition with initiator transfer RNA. The 3.35-A structure of Ksg bound to the 30S ribosomal subunit presented here provides a structural description of two Ksg-binding sites as well as a basis for understanding Ksg resistance. Notably, neither binding position overlaps with P-site tRNA; instead, Ksg mimics codon nucleotides at the P and E sites by binding within the path of the mRNA. Coupled with biochemical experiments, our results suggest that Ksg indirectly inhibits P-site tRNA binding through perturbation of the mRNA-tRNA codon-anticodon interaction during 30S canonical initiation. In contrast, for 70S-type initiation on leaderless mRNA, the overlap between mRNA and Ksg is reduced and the binding of tRNA is further stabilized by the presence of the 50S subunit, minimizing Ksg efficacy.

PubMed: 16998488
DOI: 10.1038/nsmb1145

Experimental method

X-RAY DIFFRACTION (3.35 Å)